ABSTRACT The United States government has contributed over $50 billion to expand antiretroviral therapy (ART) access in sub-Saharan Africa. As people living with HIV (PLWH) in the region realize the medical benefits of these initiatives, their AIDS-related mortality is declining and their life expectancy is increasing. Yet, these programs typically apply a narrow focus on AIDS-related health, which overlooks the drivers of quality of life for this population, and risks losing the tremendous gains achieved through investments in HIV care programs. Consequently, there is a need to identify determinants of quality of life for older PLWH in sub-Saharan Africa, and evaluate interventions to sustain wellbeing. To date, most studies of aging with HIV in the region have been cross-sectional and have focused on single morbidity domains (e.g. hypertension). There is remarkably little data about regional preferences for and determinants of quality of life for older PLWH. Our preliminary data among older PLWH in Uganda demonstrate meaningfully different medical, behavioral and inflammatory risk profiles, and outsized effects of HIV stigma on social functioning and wellbeing, compared to western settings. Similarly, we and others have shown that alterations to family structures caused by deaths due to HIV might undermine quality of life in the region. Thus, our scientific premise is that the social, biomedical, and inflammatory determinants of quality of life for older PLWH in rural sub-Saharan Africa will be different from those in the United States. Our overarching goal is to elucidate the determinants of quality of life for older PLWH in rural Uganda, and how HIV contributes to them, in order to develop effective interventions to improve quality of life for this population. In the current proposal, we will address important gaps in the field by: 1) using qualitative methods to develop a conceptual framework explaining how HIV impacts quality of life among older PLWH in Uganda, and inform measure selection for this proposal, 2) demonstrating how HIV infection affects trajectories of functioning and quality of life in rural Uganda; and 3) identifying modifiable, HIV-specific determinants of poor quality of life to promote intervention development. This research plan is relevant to the Office of AIDS Research high-priority topics and responds to multiple National Institute of Aging topic areas through its focus on: 1) interactions between HIV, social determinants, functional status and wellbeing; 2) relationships between HIV infection and cognitive functioning; and 3) geriatric approaches to assessment of older adults with HIV. While addressing these high-priority areas of investigation, our study will build research capacity by providing a platform for junior investigators at the Mbarara University of Science and Technology, as part of a training initiative with Harvard Medical School (NIH D43 TW010128). Our study is anticipated to have significant public health impact by informing selection and evaluation of interventions to improve quality of life among the large and growing population of older PLWH in rural sub-Saharan Africa.